Regio- and Stereoselective 1,3-Dipolar Cycloadditions to 6H-1,2-Oxazines Leading to New Heterobicyclic Compounds

Elmar Schmidt; Hans-Ulrich Reissig; Reinhold Zimmer

doi:10.1055/s-2006-942403

PAPER

Regio- and Stereoselective 1,3-Dipolar Cycloadditions to 6H-1,2-Oxazines Leading to New Heterobicyclic Compounds

Elmar Schmidt^a, Hans-Ulrich Reissig*^b, Reinhold Zimmer^b
^a Technische Universität Dresden, Institut für Organische Chemie, Bergstraße 66, 01069 Dresden, Germany
^b Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: hans.reissig@chemie.fu-berlin.de ;

Abstract

Alle Artikel dieser Rubrik

Abstract

Typical 1,3-dipoles such as nitrile oxides, imines and ylides, as well as diazoalkanes, nitrones and azomethine ylides generally underwent smooth [3+2] cycloadditions to 6H-1,2-oxazines. The heterobicyclic adducts were obtained in moderate to very good yields, with excellent regioselectivities and high diastereoselectivity. The 6-ethoxy substituent of the 6H-1,2-oxazines strongly shields one face and thus leads to almost exclusive formation of exo-configured products. 6H-1,2-Oxazines are therefore sufficiently reactive and selective dipolarophiles. The regioselectivity of the 1,3-dipolar cycloadditions is briefly discussed considering steric and electronic effects. PM3 calculations did not lead to fully satisfactory results in predicting the observed high regioselectivities. Preliminary subsequent reactions of the heterobicyclic products involve chemoselective reductions with sodium cyanoborohydride or hydrogen in the presence of palladium, and a decarboxylative isoxazoline fragmentation reaction, stereoselectively furnishing the 5-cyano-4-hydroxy substituted 1,2-oxazine derivative in high yield.

Key words

cycloadditions - diazo compounds - 1,2-oxazines - bicyclic compounds - diastereoselectivity - regioselectivity

Volltext

Referenzen

References

For reviews, see:

1a Gilchrist TL. Chem. Soc. Rev. 1983, 12: 53

1b Tsoungas PG. Heterocycles 2002, 57: 915

1c Tsoungas PG. Heterocycles 2002, 57: 1149

2a Zimmer R. Hiller F. Reissig H.-U. Heterocycles 1999, 50: 393

2b Buchholz M. Hiller F. Reissig H.-U. Eur. J. Org. Chem. 2002, 2838

2c Buchholz M. Reissig H.-U. Synthesis 2002, 1412

3 Homann K. Angermann J. Collas M. Zimmer R. Reissig H.-U. J. Prakt. Chem. 1998, 340: 649

4a Angermann J. Homann K. Reissig H.-U. Zimmer R. Synlett 1995, 1014

4b Zimmer R. Homann K. Angermann J. Reissig H.-U. Synthesis 1999, 1223

5 Homann K. Dissertation Technische Hochschule Darmstadt; Germany: 1994.

6 Angermann J. Dissertation Technische Universität Dresden; Germany: 1997.

7 Collas M. Dissertation Technische Universität Dresden; Germany: 1999.

8a Huisgen R. Angew. Chem. 1963, 75: 604

8b Huisgen R. Angew. Chem., Int. Ed. Engl. 1968, 7: 321 ; Angew. Chem. 1968, 80, 329

8c 1,3-Dipolar Cycloaddition Chemistry Padwa A. John Wiley and Sons Inc; New York: 1984.

8d Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products Padwa A. Pearson WH. John Wiley and Sons Inc; New York: 2002.

9a Buchholz M. Reissig H.-U. Eur. J. Org. Chem. 2003, 3524

9b Zimmer R. Orschel B. Scherer S. Reissig H.-U. Synthesis 2002, 1553

10 Huisgen R. Stangl H. Sturm HJ. Raab R. Bunge K. Chem. Ber. 1972, 105: 1258

11 Schmidt E. Reissig H.-U. Rademacher O. Z. Kristallogr. 2000, 215: 283

12 Huisgen R. Seidel M. Wallbillich G. Knupfer H. Tetrahedron Lett. 1962, 17: 3

13 Huisgen R. Stangl H. Sturm HJ. Wagenhofer H. Angew. Chem. 1962, 74: 31

14a Galley G. Pätzel M. Jones PG. Tetrahedron 1995, 51: 1631

14b Mish MR. Guerra FM. Carreira EM. J. Am. Chem. Soc. 1997, 119: 8379

15 For review, see: Podlech J. J. Prakt. Chem. 1998, 340: 679

16 For review, see: Matsumoto K. Hamana H. Iida H. Helv. Chim. Acta 2005, 88: 2033

17 Tsuge O. Kanemasa S. Yoshioka M. J. Org. Chem. 1988, 53: 1384

18a Fukui K. Fortschr. Chem. Forsch. 1970, 15: 1

18b Bastide J. El-Ghandour N. Henri-Rousseau O. Tetrahedron Lett. 1972, 13: 4225

18c Bastide J. El-Ghandour N. Henri-Rousseau O. Bull. Soc. Chim. Fr. 1973, 2290

18d Bastide J. Henri-Rousseau O. Bull. Soc. Chim. Fr. 1973, 2294

18e Sustmann R. Pure Appl. Chem. 1974, 40: 569

18f Houk KN. Acc. Chem. Res. 1975, 8: 361

18g Fleming I. Frontier Orbitals and Organic Chemical Reactions Wiley; London: 1976.

19a Stewart JJP. J. Comput. Chem. 1989, 10: 209

19b Stewart JJP. J. Comput. Chem. 1989, 10: 221

20 Schmidt E. Dissertation Technische Universität Dresden; Germany: 2001.

21 Jänicke-Rössler U. Zahn G. Hiller F. Reissig H.-U. Z. Kristallogr. 1998, 213: 261

For selected examples of pyrazole derivatives, see:

22a Upadhyay J. Dave U. Parekh H. J. Indian Chem. Soc. 1991, 68: 413

22b Camacho ME. León J. Entrena A. Velasco G. Carrión MD. Escames G. Vivó A. Acuna-Castroviejo D. Gallo MA. Espinosa A. J. Med. Chem. 2004, 47: 5641

23 Zimmer R. Arnold T. Homann K. Reissig H.-U. Synthesis 1994, 1050

24 Laganis ED. Chenard BL. Tetrahedron Lett. 1984, 25: 5831

25 Kozikowski AP. Adamczyk M. J. Org. Chem. 1983, 48: 366

26 Brüning I. Grashey R. Hauck H. Huisgen R. Seidl H. Org. Synth. 1966, 46: 127